AB inito studies of a pentacyclo-undecane cage lactam.

Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2011.Abstract available in PDF.Please refer to PDF for abstract

Experimental and Theoretical Mechanistic Investigation of the Iridium-Catalyzed Dehydrogenative Decarbonylation of Primary Alcohols

The mechanism for the iridium–BINAP catalyzed dehydrogenative decarbonylation of primary alcohols with the liberation of molecular hydrogen and carbon monoxide was studied experimentally and computationally. The reaction takes place by tandem catalysis through two catalytic cycles involving dehydrogenation of the alcohol and decarbonylation of the resulting aldehyde. The square planar complex IrCl­(CO)­(<i>rac</i>-BINAP) was isolated from the reaction between [Ir­(cod)­Cl]₂, <i>rac</i>-BINAP, and benzyl alcohol. The complex was catalytically active and applied in the study of the individual steps in the catalytic cycles. One carbon monoxide ligand was shown to remain coordinated to iridium throughout the reaction, and release of carbon monoxide was suggested to occur from a dicarbonyl complex. IrH₂Cl­(CO)­(<i>rac</i>-BINAP) was also synthesized and detected in the dehydrogenation of benzyl alcohol. In the same experiment, IrHCl₂(CO)­(<i>rac</i>-BINAP) was detected from the release of HCl in the dehydrogenation and subsequent reaction with IrCl­(CO)­(<i>rac</i>-BINAP). This indicated a substitution of chloride with the alcohol to form a square planar iridium alkoxo complex that could undergo a β-hydride elimination. A KIE of 1.0 was determined for the decarbonylation and 1.42 for the overall reaction. Electron rich benzyl alcohols were converted faster than electron poor alcohols, but no electronic effect was found when comparing aldehydes of different electronic character. The lack of electronic and kinetic isotope effects implies a rate-determining phosphine dissociation for the decarbonylation of aldehydes

Emergency care drugs' chemical stability after eight weeks’ deployment in the prehospital setting

Temperature conditions vary in emergency service vehicles, which may pose a risk to the integrity of the drugs on board, possibly rendering them ineffective and increasing morbidity and mortality in patients. Aim: This study assessed the stability of four emergency care drugs (adrenaline, etomidate, ketamine, and rocuronium) after eight weeks of deployment in the prehospital context. Methods: The study adopted a longitudinal quantitative design to evaluate the chemical stability of emergency care drugs. The study was conducted at four emergency medical service bases in Ballito, Durban and Pietermaritzburg, South Africa. The primary outcome was the relative reduction in drug concentration from the labelled concentration after four and eight weeks. High-performance liquid chromatography-mass spectrometry (HPLC-MS) analysed samples to determine the concentration of active ingredients in the drug samples. Results: HPLC analysis was done on 176 samples. The ambient temperature ranged from 18.7 to 44 °C in the first four weeks, averaging 26.8 °C ± 3.0. At 4 and 8 weeks, Adrenaline decreased 24.93 % and 22.73 %, respectively. Etomidate's control had 3.06 mg/ml, not the 2 mg/ml on the bottle. After 4 and 8 weeks, the samples had 3.10 and 3.15 mg/ml active components, respectively. Ketamine degraded over 30 % after four weeks but not beyond that. The Ketamine package states 10 mg/ml. However, we found 17.46 mg/ml. Rocuronium was 6.45 mg/ml in the control, although the manufacturer specified 10 mg/ml. At four weeks, the concentration was 6.70 mg/ml; at eight weeks, 6.56. Conclusion: This study suggests that adrenaline and ketamine degrade by more than 20 % within four weeks of deployment in the prehospital field, whereas etomidate and rocuronium remain stable after eight weeks

Facile synthesis of N-doped graphene encapsulated Ni@N/C catalyst and its catalysis for highly selective semi-hydrogenation of alkynes

Although precious transition metals such as palladium, platinum, and iridium are widely used in hydrogenation reactions, the earth-abundant transition metal-catalyzed highly selective semi-hydrogenation of terminal alkynes to terminal alkenes remains poorly developed and a challenge. Herein we demonstrate the excellent selective, cost-effective semi-hydrogenation of terminal alkynes via a novel graphene encapsulated Ni@N/C catalyst. The graphene layer encapsulated nano-catalyst Ni@N/C could significantly avoid metal leaching and improve the stability of the catalyst. The strong interaction of nitrogen with the Ni nanoparticles regulates the activity of Ni towards selective semi-hydrogenation of terminal alkynes. Substrates having un-functionalized as well as functionalized substituents, and substrates having sensitive functional groups (olefins, ketones) which pose a challenge to hydrogenate, were semi-hydrogenated with excellent conversion (up to 99%) and selectivity (up to 99%) under optimized reaction conditions

Tandem Peterson olefination and chemoselective asymmetric hydrogenation of β-hydroxy silanes

Here, we report the first Ir-N,P complex catalyzed tandem Peterson olefination and asymmetric hydrogenation of -hydroxy silanes. This reaction resulted in the formation of chiral alkanes in high isolated yields (up to 99%) and excellent enantioselectivity (up to 99% ee) under mild conditions. Modification of the reaction conditions provides a choice to transform either an olefin or the -hydroxy silane in a chemoselective manner. Additionally, based on this method, an expedient enantioselective synthesis of (S)-(+)--curcumene, from a simple ketone, was accomplished in two steps with 75% overall yield and 95% ee

Stereodivergent Synthesis of Trisubstituted Enamides : Direct Access to Both Pure Geometrical Isomers

A stereodivergent strategy has been developed to access either (E)- or (Z)-isomers of trisubstituted enamides. Starting from an extensive range of ketones, it was possible to synthesize and isolate the desired pure isomer by switching the reaction conditions. Lewis acid activation enables the formation of the (E)-isomers in high stereoselectivity (&gt;90:10) and good yields. On the other hand, the use of a Bronsted acid allows the preparation of the (Z)-isomers, again in high selectivity (up to 99:1), with moderate yields

Asymmetric Hydrogenation of Allylic Alcohols Using Ir-N,P-Complexes

In this study, a series of gamma,gamma-disubstituted and beta,gamma-disubstituted allylic alcohols were prepared and successfully hydrogenated using suitable N,P-based Ir complexes. High yields and excellent enantioselectivities were obtained for most of the substrates studied. This investigation also revealed the effect of the acidity of the N,P-Ir-complexes on the acid sensitive allylic alcohols. DFT Delta pK(a) calculations were used to explain the effect of the N,P-ligand on the acidity of the corresponding Ir-complex. The selectivity model of the reaction was used to accurately predict the absolute configuration of the hydrogenated alcohols

Regioselective Iridium-Catalyzed Asymmetric Monohydrogenation of 1,4-Dienes

A highly efficient regio- and enantioselective monohydrogenation of 1,4-dienes has been realized using an iridium catalyst with a chiral N,P-ligand under mild conditions. The substrate scope was studied and included both unfunctionalized as well as functionalized substituents on the meta- or para-position. Substrates having substituents with functionalities such as silyl protected alcohols or ketals were monohydrogenated in high regioselectivity and high enantiomeric excess (up to 98% ee)

Facile synthesis of controllable graphene-co-shelled reusable Ni/NiO nanoparticles and their application in the synthesis of amines under mild conditions

The primary objective of many researchers in chemical synthesis is the development of recyclable and easily accessible catalysts. These catalysts should preferably be made from Earth-abundant metals and have the ability to be utilised in the synthesis of pharmaceutically important compounds. Amines are classified as privileged compounds, and are used extensively in the fine and bulk chemical industries, as well as in pharmaceutical and materials research. In many laboratories and in industry, transition metal catalysed reductive amination of carbonyl compounds is performed using predominantly ammonia and H-2. However, these reactions usually require precious metal-based catalysts or RANEY (R) nickel, and require harsh reaction conditions and yield low selectivity for the desired products. Herein, we describe a simple and environmentally friendly method for the preparation of thin graphene spheres that encapsulate uniform Ni/NiO nanoalloy catalysts (Ni/NiO@C) using nickel citrate as the precursor. The resulting catalysts are stable and reusable and were successfully used for the synthesis of primary, secondary, tertiary, and N-methylamines (more than 62 examples). The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, and H-2 under very mild industrially viable and scalable conditions (80 degrees C and 1 MPa H-2 pressure, 4 h), offering cost-effective access to numerous functionalized, structurally diverse linear and branched benzylic, heterocyclic, and aliphatic amines including drugs and steroid derivatives. We have also demonstrated the scale-up of the heterogeneous amination protocol to gram-scale synthesis. Furthermore, the catalyst can be immobilized on a magnetic stirring bar and be conveniently recycled up to five times without any significant loss of catalytic activity and selectivity for the product